Development of cyclobutene- and cyclobutane-functionalized fatty acids with inhibitory activity against Mycobacterium tuberculosis

Authors

Wantanee Sittiwong, University of Nebraska - Lincoln
Denise Zinniel, University of Nebraska-LincolnFollow
Robert J. Fenton, University of Nebraska - LincolnFollow
Darrel Marshall, University of Nebraska - Lincoln
Courtney B. Story, University of Nebraska-Lincoln
Bohkyung Kim, University of Connecticut, Storrs
Ji-Young Lee, University of Connecticut, StorrsFollow
Robert Powers, University of Nebraska-LincolnFollow
Raul G. Barletta, University of Nebraska - LincolnFollow
Patrick Dussault, University of Nebraska-LincolnFollow

Date of this Version

2014

Citation

ChemMedChem. 2014 August ; 9(8): 1838–1849. doi:10.1002/cmdc.201402067.

Comments

© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Abstract

Eleven fatty acid analogs incorporating four-membered carbocycles (cyclobutenes, cyclobutanes, cyclobutanones, and cyclobutanols) were investigated for the ability to inhibit growth of Mycobacterium smegmatis (Msm) and Mycobacterium tuberculosis (Mtb). A number of the analogs displayed inhibitory activity against both mycobacterial species in minimal media. Several of the molecules displayed potent levels of inhibition against Mtb with MIC values equal to or below those obtained with the anti-tuberculosis drugs D-cycloserine and isoniazid. In contrast, two of the analogs displaying the greatest activity against Mtb failed to inhibit E. coli growth under either set of conditions. Thus, the active molecules identified here (1, 2, 6, and 8) may provide the basis for development of anti-mycobacterial agents against Mtb.